XARELTO 10 10MG TABLET

Indications

• Prophylaxis of venous thromboembolism following knee replacement surgery
• Prophylaxis of venous thromboembolism following hip replacement surgery
• Treatment of deep vein thrombosis
• Treatment of pulmonary embolism

Dosage

Adults: For the prophylaxis of venous thromboembolism following knee replacement surgery: 10 mg once daily for 2 weeks, starting 6–10 hours

Mechanism of action

Rivaroxaban competitively inhibits both free and clot-bound factor Xa. Factor Xa is essential for the conversion of prothrombin to thrombin, which is necessary for fibrinogen to be activated into fibrin, leading to clot formation. By inhibiting factor Xa, rivaroxaban effectively terminates the amplification of thrombin generation, preventing thrombus formation. Its action is irreversible and does not require a cofactor, distinguishing it from other anticoagulants like heparin.

Pharmacodynamics

Rivaroxaban exhibits anticoagulant properties by directly binding to factor Xa. This binding prevents the activation of prothrombin, thereby blocking the coagulation cascade and thrombus formation. Unlike traditional anticoagulants, rivaroxaban does not utilize antithrombin III to exert its effects, and it is administered orally, making it more convenient compared to parenteral anticoagulants.

Pharmacokinetics

Rivaroxaban is rapidly absorbed and reaches peak plasma concentrations within 2-4 hours after oral administration. It is extensively metabolized in the liver, primarily by CYP3A4 and CYP2J2, and is also a substrate for P-glycoprotein. The half-life of rivaroxaban is approximately 5-9 hours in healthy individuals, and it is excreted via both renal and fecal routes, with about 66% excreted as metabolites and 28% as unchanged drug.

Contra-indications

• Active bleeding
• Bacterial endocarditis
• Active gastrointestinal ulcer

Adverse effects

• Anaemia
• Haemorrhage
• Chest pain
• Dyspnoea
• Fever
• Hepatic function abnormality
• Nausea
• Oedema
• Platelet abnormalities
• Thrombocytopenia
• Vomiting
• Wound secretion
• Anxiety
• Confusion
• Constipation
• Cough
• Diarrhoea
• Dizziness
• Drowsiness
• Fatigue
• Gastritis
• Gastrointestinal discomfort
• Genital oedema
• Headache
• Hyperbilirubinaemia
• Hypersensitivity
• Hypokalaemia
• Hypotension
• Leg pain
• Post procedural infection
• Syncope
• Vasodilation
• Vertigo

Interactions

• tucatinib+rivaroxaban: Moderate (increases exposure)
• vemurafenib+rivaroxaban: Moderate (increases exposure)
• antiarrhythmics+rivaroxaban: Unknown (increases exposure)
• antiepileptics (carbamazepine, phenobarbital, phenytoin, primidone)+rivaroxaban: Unknown (decreases exposure)
• ciclosporin+rivaroxaban: Unknown (increases exposure)
• mitotane+rivaroxaban: Unknown (decreases exposure)
• NNRTIs+rivaroxaban: Unknown (decreases exposure)
• St. John's Wort+rivaroxaban: Unknown (decreases exposure)

Precautions

• Elderly patients
• Low body weight
• Spinal or epidural anaesthesia (risk of spinal haematoma)
• Patients with a history of bleeding disorders
• Patients undergoing percutaneous coronary intervention
• Patients with renal impairment

Pregnancy

Manufacturer advises to avoid unless potential benefit outweighs possible risk-no information available.

Breast-feeding

Present in milk in animal

Mechanism of action

Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible. Rivaroxaban, an oral, direct activated factor X (Xa) inhibitor, is an anticoagulant. Factor Xa plays a central role in the blood coagulation cascade by serving as the convergence point for the intrinsic and extrinsic pathways; inhibition of coagulation factor Xa by rivaroxaban prevents conversion of prothrombin to thrombin and subsequent thrombus formation. Rivaroxaban inhibits both free and prothrombinase-bound factor Xa. Unlike fondaparinux, heparin, and the low molecular weight heparins, rivaroxaban binds directly to the active site of factor Xa without the need for a cofactor (e.g., antithrombin III). Rivaroxaban inhibits factor Xa with more than 100,000-fold greater selectivity than other biologically important serine proteases (e.g., thrombin, trypsin, plasmin, factor VIIa, factor IXa, urokinase, activated protein C). Xarelto is an orally bioavailable factor Xa inhibitor that selectively blocks the active site of factor Xa and does not require a cofactor (such as Anti-thrombin III) for activity. Activation of factor X to factor Xa (FXa) via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation.

Pharmacodynamics

Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban.